Gaucher's disease is a sphingolipid storage disease which presents generally in two clinical forms: (1) the more common adult variety in which there is primarily visceral organ and bone involvement and (2) a rare infantile form which involves the central nervous system and which runs an early fatal course. In each case, the accumulation of glucocerebroside in involved organs is due to a deficiency of the lysosomal enzyme, beta-glucocerebrosidase. The primary objective of the current proposal is to carry out extensive comparative analysis of the kinetic and physical-chemical properties of beta-glucocerebrosidase from human brain and liver. Particular emphasis will be placed on the role of natural membrane lipids in the beta-glucocerebrosidase reaction. Finally, the structure of the two unusual (9,500 and 80,000 daltons) glycoproteins that occur in tissues of patients with Gaucher's disease will be investigated. These studies may provide a molecular basis for the differences between the infantile and adult types of Gaucher's disease and should aid in the identification of therapeutically effective procedures.